This mouse was grown from its mother's skin cells

For the first time, researchers have grown eggs entirely in a lab
dish.

Skin-producing cells called fibroblasts from the tip of an adult
mouse’s tail have been reprogrammed to make eggs, Japanese researchers
report online October 17 in Nature. Those eggs were fertilized
and grew into six healthy mice. The accomplishment could make it
possible to study the formation of gametes — eggs and sperm — a
mysterious process that takes place inside fetuses. If the feat
can be repeated with human cells, it could make eggs easily
available for research and may eventually lead to infertility
treatments.

“This is very solid work, and an important step in the field,”
says developmental biologist Diana Laird of the University of
California, San Francisco, who was not involved in the study.
But, she cautions, “I wouldn’t want patients who have infertility
to think this can be done in humans next year,” or even in the
near future.

Stem cells reprogrammed from adult body cells have been coaxed
into becoming a wide variety of cells. But producing eggs, the
primordial cells of life, is far trickier. Egg cells are the
ultimate in flexibility, able to create all the bits and parts of
an organism from raw genetic instructions. They are far more
flexible, or potent, than even the embryonic-like stem cells from
which the researchers created them.

Making eggs in a dish is such a difficult task that it required a
little help from ovary cells that support egg growth, stem cell
researcher Katsuhiko Hayashi of Kyushu University in Fukuoka,
Japan, and colleagues found. The team had previously reprogrammed
stem cells to produce primordial germ cells, the cells that give
rise to eggs. But they had to put those cells into mice to finish
developing into eggs in the ovary (SN: 11/3/12, p. 14).

It’s unclear how support cells in ovaries foster egg development,
Hayashi says. Something made by support cells or physical contact
with them, or both, may be necessary for the egg to fully mature.
Researchers can’t yet reproduce the supporting cells in the lab
and so need to get those cells from embryos, Hayashi says. That
could be a problem when trying to replicate the experiments in
humans.

Hayashi and colleagues made artificial ovaries to incubate the
lab-grown eggs by extracting ovarian support cells from albino
mouse embryos. The researchers then mixed in primordial germ
cell‒like cells created from tail-tip skin cells from a normally
pigmented mouse. After 11 days in the lab dish, the eggs were
mature and ready for fertilization. That’s about the same time it
takes for eggs to mature in a mouse ovary, Laird says. That means
researchers may need patience to make human eggs in lab dishes.
“It could be a nine- to 12-month differentiation process in
humans,” she says.

Researchers fertilized the eggs and transplanted the embryos into
the uteruses of female mice. In that experiment, six pups with
dark eyes were born, indicating that they came from the tail-tip
eggs and not eggs accidently extracted from the albino mice along
with the support cells. The baby mice grew up apparently healthy
and have produced offspring of their own.

Growing quality eggs in the lab may be an all-or-nothing
exercise. In another experiment using eggs made from embryonic
stem cells, the researchers found that some genes weren’t turned
on or off as in normal eggs. And only 11 of 316 embryos made from
those lab-grown eggs grew into mouse pups. Some of the embryos
didn’t make it because they had abnormal numbers of chromosomes,
indicating that the eggs weren’t divvying up their DNA properly.

The low success rate implies that only one in every 20 lab-grown
eggs, or oocytes, is viable, Hayashi says. “This means that it is
too preliminary to use artificial oocytes for clinical purposes.
We cannot exclude a risk of having a baby with a serious disease.
We still need to do basic research to refine the culture
conditions.”